The aim of this proposal is to test new approaches to the control of fibroproliferative inflammation in the lung induced by silica and related dust. It is proposed that silica labilizes macrophage lysosomes by inducing lipid peroxidation (l.p.). Thus, agents limiting l.p., such as vitamin E and zinc, should ameliorate the dynamics of lung-fibrosis development. The extent of fibrosis of silicotic lungs correlates with the magnitude of necrosis. Two new methods are suggested to control the necrosis: using antimacrophage serum to eliminate or decrease the participation of macrophages in the inflammatory lesion and using high doses of zinc to inhibit macrophage mobility and phagocytosis. The second method is based on our original contribution which further indicates that zinc stabilizes biomembranes, thus changing the reactivity of the lung tissue against noxious agents. Furthermore, it is proposed that it is not the amount of collagen but the extent of collagen polymerization which interferes with an organ function; thus, controlling collagen crosslinking by either beta-aminopropionitrile (BAPN) or D-penicillamine or administering high amounts of zinc should protect the functional deterioration of the lungs during the development of silicosis. It is suggested that stabilization of biomembranes is the mechanism by which to increase the resistance of tissues against injurious agents (silica, asbestos). This could be achieved by zinc treatment, and the possibility that polyvinyl-pyridine-N-oxide (PVPO) stabilizes biomembranes will also be explored. A multidisciplinary, complex approach to the problems of lung injury and fibrosis will be taken, evaluating various membranes' status, cells (microphage, fibroblast) reactivity, and connective tissue (collagen) metabolism. The final goal is to present a scientifically sound proposal for using some new agents (zinc, BAPN, anti-oxidants) in the treatment of fibrotic lesion of the lung.